1. Field of the Invention
The present invention relates to a filter for selectively removing leukocytes. More particularly, the present invention is concerned with a filter for selectively removing leukocytes from human whole blood, which comprises a filter substrate having coated thereon a hydrophilic synthetic polymer in a coating ratio of 70% or more with respect to the overall surface of the filter substrate, wherein the polymer has a specific weight average molecular weight. By the use of the filter of the present invention, it becomes possible to efficiently remove leukocytes (which are causative of various side effects of a transfusion) from human whole blood while holding down a loss of plasma, red cells and platelets. Therefore, the filter of the present invention is extremely useful for the production of blood products. The present invention is also concerned with a method for selectively removing leukocytes from human whole blood, using the above-mentioned filter.
2. Prior Art
At present, the conventional whole blood transfusion has come to be replaced by the blood component transfusion wherein only a blood component necessary for treating a particular disease of the patient is transfused while suppressing the transfusion of an unnecessary blood component to a minimum.
Examples of blood component transfusions include red cell transfusion, platelet transfusion, plasma transfusion and the like. In many cases of the red cell transfusion (which is performed on a patient who needs supplementation of red cells), a red cell concentrate is administered. In many cases of the platelet transfusion (which is performed on a patient who needs supplementation of platelets), a platelet concentrate is administered.
As a problem accompanying the transfusion, there can be mentioned side effects of a transfusion. The blood component transfusion is considered to be one of the measures effective for avoiding the side effects of a transfusion. However, it is known that various side effects are caused even by a blood component transfusion. For example, it has been reported that in a patient who has received a transfusion of a platelet concentrate, a wide variety of side effects may occur, such as non-hemolytic feverish reaction, alloimmune reaction, post-transfusion acute lung injury, graft versus host disease (GVHD), allergic reaction, anaphylactic reaction, viral and bacterial infections and immunosuppression.
It is considered that most of these side effects of a transfusion are caused by leukocytes contained in the blood products employed. Therefore, leukocytes contained in a blood product should be removed so that the number of the leukocytes in the blood product is lowered to a level which does not cause side effects of a transfusion.
Examples of methods for removing leukocytes from a leukocyte-containing cell suspension (such as blood) include:                a centrifugation method in which a cell suspension is subjected to centrifugation to thereby separate and remove leukocytes;        a filtration method in which a cell suspension is subjected to filtration to thereby cause the leukocytes contained in the cell suspension to be adsorbed on the filter; and        a dextran method in which a dextran-containing physiological saline is added to and mixed with a cell suspension placed in a blood bag to obtain a mixture having a floating leukocyte layer, and the leukocyte layer is removed by suction.        
Of these methods for removing leukocytes, the filtration method is widely employed due to its advantages that the ability to remove leukocytes is high, the operation is easy and the cost is low.
Various reports have been made with respect to a filter for removing leukocytes. For example, Japanese Patent Application Laid-Open Specification No. 60-193468 discloses a filter for removing leukocytes, which exhibits high efficiency in the removal of leukocytes and can treat blood at an increased rate. This filter comprises a filter material which is a non-woven fabric having a specific fiber diameter and a specific bulk density. However, although this filter is excellent in the leukocyte removal efficiency, the platelet passage ratio of this filter is not satisfactory.
For solving such problem, various studies have conventionally been made in which a coating is formed on a filter substrate in an attempt to simultaneously improve both the leukocyte removal efficiency and the platelet passage ratio with respect to a leukocyte removing filter. However, in any of these studies, it was found that at least one of the leukocyte removal efficiency and the platelet passage ratio is not satisfactory.
For example, Japanese Patent Application Laid-Open Specification No. 55-129755 discloses a method for collecting leukocytes and lymphocytes in a form containing only a small amount of red cells and platelets, wherein the method uses a filter which comprises a filter material which is a non-woven fabric comprising fibers coated with an antithrombogenic material, such as a polyether urethane, poly(hydroxyethyl methacrylate) or silicone. However, this filter has a problem in that the leukocyte removal ratio is low.
Japanese Patent Application Laid-Open Specification No. 60-119955 discloses that platelets are extremely unlikely to be adsorbed on a polymer containing a nitrogen-containing basic functional group and having a nitrogen content of from 0.05 to 3.5% by weight. However, this patent document has no disclosure with respect to the affinity of leukocytes to the above-mentioned polymer (i.e., adsorbability of leukocytes on the above-mentioned polymer).
Examined Japanese Patent Application Publication No. 6-51060 (corresponding to U.S. Pat. No. 4,936,998) describes that, with respect to a fiber which contains, in a peripheral surface portion thereof, a nonionic hydrophilic group and a nitrogen-containing basic functional group, platelets are unlikely to be adsorbed on the fiber, whereas leukocytes are likely to be adsorbed on the fiber. This patent document discloses a filter for removing leukocytes, which comprises a filter material which is a non-woven fabric comprising the above-mentioned fiber. Further, this patent document describes that when the above-mentioned filter is used for the treatment of bovine blood, the above-mentioned filter exhibits excellent leukocyte removal efficiency and high platelet passage ratio. However, although this filter exhibits excellent removal efficiency for human leukocytes, this filter is unsatisfactory in the passage ratio of human platelets. In this connection, it should be noted that the low platelet passage ratio of this filter has not been particularly considered as being a problem. The reason for this is that, when this filter is used for the treatment of a platelet concentrate (having high platelet content), still a great amount of platelets can be passed through this filter, so that the platelet passage ratio of this filter is acceptable. On the other hand, however, in the case of the use of this filter for the treatment of human whole blood (having a platelet content lower than that of a platelet concentrate), the platelet passage ratio of this filter is not acceptable.
Japanese Patent No. 2854857 discloses a filter for removing leukocytes, comprising, as a filter material, a non-woven fabric of polyethylene terephthalate, which is coated with chitosan or a derivative thereof. However, when this filter is used for the treatment of human whole blood, although this filter exhibits high platelet passage ratio and high red cell passage ratio, the leukocyte removal efficiency of this filter is extremely low. That is, the leukocyte removing performance of this filter is not satisfactory.
In the production of the conventional filters for removing leukocytes (such as those filters mentioned above), a coating solution having dissolved therein a relatively small amount of a coating material is used, so that the amount of the coating material which covers the surface of the filter substrate of the filter is relatively small. The reasons why a coating solution containing a relatively small amount of a coating material is conventionally used are explained below.
The reason 1 is as follows. A coating material used for producing a leukocyte removing filter is relatively expensive. Therefore, the use of an increased amount of a coating material leads to an increase in the production cost of the filter.
The reason 2 is as follows. When the concentration of a coating material contained in the coating solution is high, the viscosity of the coating solution becomes high, so that uniform coating of the filter substrate with the coating solution becomes difficult.
The reason 3 is as follows. When a hydrophilic polymer is used as a coating material and when the amount of the hydrophilic polymer used is large, it is considered that some water-soluble component will be dissolved-out from the coating material and enter a cell suspension (which has been treated with the filter). It is possible that when the cell suspension containing the water-soluble component is administered to a human body, the water-soluble component exhibits a toxicity.
Further, the above-mentioned Japanese Patent No. 2854857 describes that when a coating solution having a high concentration of a coating material is used, the leukocyte removal ratio of the resultant filter tends to be lowered.
For these reasons, as mentioned above, the amount of the coating material used for producing the conventional filters is relatively small. Therefore, it is considered that in the conventional leukocyte removing filters, a considerably large portion of the surface of the filter substrate remains uncoated. However, the relationship between the coating ratio of the surface of the filter substrate and the performance (i.e., the leukocyte removal efficiency and the platelet passage ratio) of the filter is conventionally not known at all.